Recognition of antigen by T cells involves an interaction between parts of the T cell receptor and an antigenic complex of self-major histocompatibility complex protein and peptide derived from a foreign protein. This interaction is of relatively weak affinity. In this project, soluble forms of the T cell receptor will be produced and used to measure the interaction. The ligand in question is a purified soluble form of the MHC class I protein, bound to an individual specific peptide. The interaction will be measured using surface plasmon resonance techniques. Previous studies have identified analogues of the peptide antigen that are antagonistic to the antigenic peptide. In addition, peptides that produce positive and negative selection in the thymus have been identified. The residues of the antigenic peptide that are important for interaction with the MHC and with the T cell receptor have been determined. Comparison will be made between the affinity of the TCR for MHC with these antigen analogues, in order to determine the role of affinity in activation of T cells, and in maturation of T cells in the thymus. This will give information on how the development or activation of T cells can be modulated by specific peptides, which may prove useful in prophylaxis or treatment of autoimmune disorders. Recognition of ligand by the T cell receptor results in initiation of a signaling cascade that activates the T cell. It is now known how this pathway is initiated by the receptor. The recognition event is transmitted in some way to other parts of the TCR complex, the CD3 molecules. This project will show to what extent TCR signaling is a qualitative or quantitative event.